Partial recovery of the left DLPFC-right insula circuit with reduced carving in abstinent heroin users: a longitudinal study

Abstract Background Brain recovery phenomenon after long-term abstinence had been reported in substance use disorders. Yet, few longitudinal studies have been conducted to observe the potential recovery in heroin users, and little is known about the neural mechanism underlying the decreased craving after prolonged abstinence. Methods The 8-month longitudinal design was carried out for 29 heroin users and 30 healthy controls. By choosing the L_DLPFC activated by heroin cue as seeding region, the different brain connections patterns were compared between HCs and HUs by using Granger causality analysis (GCA) at baseline. Then paired t-test was employed to detect the potential recovery of L_DLPFC circuits after prolonged abstinence. Visual analog scale (VAS) and trail-making test-A (TMT-A) were adopted to investigate craving and cognitive control impairments, respectively. The neuroimaging changes were then correlated with the behavioral improvements. Similar analyses were applied for the mirrored right DLPFC to verify the lateralization hypothesis of the DLPFC in addiction. Results In the longitudinal study, enhanced GCA coefficients were observed in the L_DLPFC-R_insula circuit in heroin users after long-term abstinence, which were associated with craving score changes. At baseline, decreased GCA coefficients from left DLPFC to bilateral SMA and right putamen, together with the reduced GCA strength from bilateral OFC to left DLPFC were found between HUs and HCs. Conclusion Our findings extended the brain recovery phenomenon into heroin fields and suggested the increased regulation of the L_DLPFC over the insula after prolonged abstinence was important for craving inhibition.